Clinical studies of workers exposed chronically to cadmium (Cd) suggest that Cd exposure may result in anosmia. Chronic exposure to Cd in adult rats has been found to cause an increased uptake of Cd in the olfactory bulb. These two lines of evidence suggest that chronic Cd exposure might impair olfaction. Zinc (Zn) has been suggested to play a role in maintaining olfactory function. The mechanisms of toxic action of Cd has been attributed to the interaction of Cd with Zn in many organ systems. The purpose of the proposed project is to determine what effects chronic low-level exposure to Cd (via inhalation) may have on the rat olfactory system, and by what mechanisms Cd exerts any observed toxic action. The proposed project will determine whether exposure of rats to chronic low levels of Cd via inhalation impairs olfactory function (i.e., increases the olfactory threshold) in a dose-related fashion. This will be accomplished by using the conditioned suppression technique. Exposure levels were selected so as to permit comparison of the development of deficits in olfactory function with the development of early renal damage. Histological alterations in the olfactory system will be examined by light microscopy. Alterations in odor thresholds and histology will be correlated with Cd and Zn content in the olfactory bulb. The proposed project will also determine whether Cd-induced impairment in olfaction is reversible. Finally, the role of the interaction of Cd with Zn in mediating olfactory effects of Cd will be studied. The proposed project will not only provide useful and necessary information for the evaluation of the recommended TLV for Cd, but will also help elucidate the mechanisms of toxic action for this agent, as well as serve as a technique which may be useful in assessing the olfactory effects of other toxic compounds.